Huntington Medical Research Institutes

DYSFUNCTION OF SODIUM HOMEOSTASIS IN A RAT MIGRAINE MODEL

NOVEL DEVELOPMENTAL PATHWAYS UNDERLYING PSYCHIATRIC DISORDERS

COGNITIVE CHALLENGE TO REVEAL SYSTEMIC NEUROPHYSIOLOGY BIOMARKERS IN PRE-SYMPTOMATIC ALZHEIMER?S DISEASE - THE BURDEN ON ALZHEIMER’S DISEASE (AD) IS GROWING DUE TO LONGER LIFE SPAN AND LACK OF EFFECTIVE TREATMENT. THE KNOWLEDGE GAP EXISTS FOR EARLY DETECTION AND PREDICTION OF SYMPTOM ONSET. AD PATHOLOGY (AMYLOID/TAU) AND SYNAPTIC DYSFUNCTION PRECEDES SYMPTOMS BY DECADES AND OFFERS A WINDOW OF OPPORTUNITY FOR EARLY AD DETECTION. CURRENT EARLY AD DIAGNOSIS DEPENDS ON EXPENSIVE IMAGING OR INVASIVE CEREBROSPINAL FLUID (CSF) DETECTION OF AMYLOID/TAU. OUR GOAL IS TO IDENTIFY NON-INVASIVE BIOMARKERS THAT FILL THIS GAP WITH SIMPLE TESTS BENCHMARKED TO AMYLOID/TAU BIOMARKERS. OUR EARLY STUDIES DEFINED PRE-SYMPTOMATIC AD: ELDERLY STUDY PARTICIPANTS WERE CLASSIFIED AS COGNITIVELY HEALTHY (CH) IN A MULTI-DOMAIN, NEUROPSYCHOMETRIC BATTERY. WE CLASSIFY CH PARTICIPANTS INTO TWO GROUPS BASED ON A REGRESSION-DERIVED CSF ASS42/TAU RATIO CUTOFF: CH INDIVIDUALS WITH PATHOLOGICAL RATIO (CH-PAT) OR WITH NORMAL RATIO (CH-NAT). AFTER 4 YEARS, 40% OF CH-PAT BUT NO CH-NAT INDIVIDUALS DECLINED COGNITIVELY, PROVIDING A STRONG COHORT TO EVALUATE BIOMARKERS FOR PRE- SYMPTOMATIC AD (CH-PATS) FROM NORMAL AGING (CH-NATS). AD AFFECTS MULTIPLE NERVOUS SYSTEMS. TIGHTLY RELATED TO OUR HEALTH, THE INTERACTIONS BETWEEN CONSCIOUS EXECUTIVE FUNCTION, SUBLIMINAL PROCESSING, AND AUTONOMIC REGULATION (CSA SYSTEM) RESPOND TO INTERNAL AND EXTERNAL STIMULI WITH NEURAL OSCILLATIONS THAT ARE AFFECTED BY SYNAPTIC DYSFUNCTIONS. THE CSA NEURAL OSCILLATIONS CAN BE DETECTED BY NON-INVASIVE ELECTROPHYSIOLOGICAL METHODS: EEG AND ECG, BENCHMARKED TO AMYLOID/TAU. INDIVIDUAL CSA DYSFUNCTIONS HAVE BEEN REPORTED IN THE MILD COGNITIVE IMPAIRMENT STAGE, WHILE CSA HAS NOT BEEN STUDIED IN THE PRE-SYMPTOMATIC AD. WE HYPOTHESIZED THAT CSA SYSTEM MEASUREMENTS COMBINE TO PROVIDE ROBUST BIOMARKERS FOR PRE-SYMPTOMATIC AD. ANALOGOUS TO THE STRESS TEST TO UNMASK CORONARY INSUFFICIENCY, OUR COGNITIVE CHALLENGE REVEALED CH-PATS HAD FRONTAL HYPER-ACTIVITIES WITH LOW LOAD CHALLENGE AND INSUFFICIENT COGNITIVE RESOURCES WITH HIGH LOAD CHALLENGES, HYPERRESPONSIVITY TO SUBLIMINAL INTERFERENCE, AND HYPERACTIVE AUTONOMIC REGULATION. FURTHER, COMBINED CSA BIOMARKERS IMPROVE DETECTION OF PRE-SYMPTOMATIC AD. THEREFORE, WE HYPOTHESIZE THAT NEURAL OSCILLATIONS DURING COGNITIVE CHALLENGE WILL REVEAL ALTERED EXECUTIVE FUNCTIONS IN PRE-SYMPTOMATIC AD, CORRELATE WITH COMPROMISED SUBLIMINAL PROCESSING AND AUTONOMIC NERVOUS FUNCTION, AND THEIR COMBINATION WILL IMPROVE DETECTION AND PREDICTION OF PRE-SYMPTOMATIC AD. OUR SPECIFIC AIMS WILL TEST OUR HYPOTHESIS IN A NEW COHORT AND TEST THE ABILITY OF CSA BIOMARKERS TO IDENTIFY CH- PATS AND PREDICT DECLINE IN A 2-YEAR LONGITUDINAL STUDY. ACCOMPLISHING THIS CSA APPROACH WILL PROVIDE MULTIPLE NOVEL TRANSLATIONAL BIOMARKERS TO CHARACTERIZE PRE-SYMPTOMATIC AD. THESE BIOMARKERS ARE NON-INVASIVE, BENCHMARKED TO ESTABLISHED CSF BIOMARKERS. OUR RESEARCH ADDRESSES AN IMPORTANT GAP IN PRE-SYMPTOMATIC AD DETECTION AND PREDICTION OF AD SYMPTOM ONSET.

ROLE OF PHLPP IN THE HEART

MONITORING NEUROCOGNITIVE PERFORMANCE AND ELECTROPHYSIOLOGICAL ACTIVITY AFTER MILD TRAUMATIC BRAIN INJURY (MTBI)

RESILIENCE, CULTURAL ALIGNMENT, AND SOCIAL SUPPORT IN BRAIN AGING: DATA FROM THE STRONG HEART STUDY

BILINGUALISM AS A PROTECTIVE FACTOR OF ADRD IN AMERICAN INDIAN ADULTS: THE STRONG HEART STUDY - PROJECT SUMMARY/ABSTRACT AMERICAN INDIAN POPULATIONS HAVE GREATER BURDEN OF CEREBROVASCULAR AND ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) COMORBIDITIES COMPARED WITH NON-HISPANIC WHITE U.S. POPULATIONS AND MAY ALSO HAVE GREATER BURDEN OF COGNITIVE DECLINE AND DEMENTIA. BILINGUALISM—COMMON IN AMERICAN INDIAN COMMUNITIES— MAY ENHANCE WORKING MEMORY CAPACITY, ATTENTIONAL CONTROL, AND COGNITIVE RESERVE, THUS REDUCING COGNITIVE RISK. HOWEVER, BILINGUALISM IS A HIGHLY INDIVIDUAL EXPERIENCE, AND THE CONTEXT OF USE CAN MODIFY ITS COGNITIVE EFFECTS. FACTORS THAT MAY INFLUENCE THIS ASSOCIATION INCLUDE AGE, SEX, VOCABULARY, PHYSICAL AND MENTAL STATUS, SOCIOECONOMIC STATUS, CULTURE, AND SOCIAL ACTIVITY. COMPREHENSIVELY ASSESSING THE RELATIONSHIP BETWEEN BILINGUALISM AND COGNITIVE PERFORMANCE MAY BE CRITICAL TO FULLY UNDERSTANDING ADRD IN AMERICAN INDIAN ADULTS. ALTHOUGH THE LINK BETWEEN BILINGUALISM AND COGNITIVE RESERVE HAS BEEN STUDIED IN MANY POPULATIONS, BILINGUALISM RESEARCH IN AMERICAN INDIAN POPULATIONS HAS BEEN LIMITED, DUE IN PART TO CRITICAL COFACTORS RELATED TO THEIR EXPERIENCES, PERSPECTIVES, AND STANDARDIZED ASSESSMENTS. UNJUST UNITED STATES (U.S.) FEDERAL POLICIES AFFECTING AMERICAN INDIAN PEOPLE INCLUDED FORCED ATTENDANCE AT ENGLISH-SPEAKING BOARDING SCHOOLS WHERE USE OF NATIVE LANGUAGES WAS PUNISHED, AND CULTURAL ASSIMILATION WAS PRIORITIZED OVER QUALITY OF EDUCATION. AS A RESULT, BILINGUALISM IN AMERICAN INDIAN ADULTS WHO ATTENDED SUCH SCHOOLS MAY PRESENT DIFFERENTLY THAN FOR OTHER POPULATIONS. INDEED, NIA (RFA-AG-23-001) DEFINES BILINGUALISM AS “PROFICIENCY IN TWO OR MORE LANGUAGES”, HOWEVER NO VALIDATED, DETAILED ASSESSMENT OF PROFICIENCY EXISTS FOR U.S. NATIVE LANGUAGES, OR FOR AMERICAN INDIAN SPEAKERS OF THOSE LANGUAGES. OUR PROPOSED STUDY WILL BE THE FIRST TO CULTURALLY ADAPT A LANGUAGE USE AND HISTORY INSTRUMENT IN A LARGE, HETEROGENEOUS AMERICAN INDIAN POPULATION. IN RESPONSE TO RFA-AG-23-001, WE WILL LEVERAGE THE STRONG HEART STUDY, A LARGE, LONGITUDINAL, HETEROGENEOUS, POPULATION-BASED STUDY OF AGING IN AMERICAN INDIAN ADULTS OVER 3 GEOGRAPHIC REGIONS (N=2,500). IN THIS PROPOSED WORK, WE WILL BUILD ON THIS STUDY, AS WELL AS OUR PRIOR WORK, TO ASSESS THE CONTINUUM OF BILINGUALISM IN AMERICAN INDIAN PEOPLES BY CULTURALLY ADAPTING THE LANGUAGE HISTORY QUESTIONNAIRE, EVALUATE BILINGUALISM IN AMERICAN INDIANS OF MULTIPLE GENERATIONS IN ASSOCIATION WITH A DETAILED COGNITIVE PERFORMANCE BATTERY, AND CONSTRUCT CONCEPTUAL MODELS TO ASSESS INTERVARIABLE RELATIONSHIPS INCLUDING EFFECT MODIFICATION AND MODERATION BY CRYSTALLIZED COGNITION. THIS PROJECT WILL ILLUMINATE QUESTIONS OF PUBLIC HEALTH SIGNIFICANCE IN A VULNERABLE POPULATION THAT REMAINS UNDERREPRESENTED IN ADRD RESEARCH, WITH POTENTIAL IMPLICATIONS FOR FUTURE PREVENTION AND TREATMENT STRATEGIES.

THE EFFECT OF ELECTRONIC CIGARETTES ON YOUNG VERSUS OLD NORMAL HEARTS AND PATHOLOGIC HEARTS

CONFIGURING MICROELECTRODES FOR SAFE AND EFFECTIVE CHRONIC ELECTRICAL STIMULATION

APPLICATION OF COMBINED CARDIOPROTECTIVE AGENTS TO PRESERVE ORGAN FUNCTION AND IMPROVE SURVIVAL DURING EXPERIMENTAL HEMORRHAGIC SHOCK

ADVANCED TECHNOLOGY FOR NEURAL INTERFACES BASED ON MICROSTIMULATION

CHRONICALLY-IMPLANTED MICROELECTRODE ARRAYS AND THEIR STABILITY

TECHNOLOGY FOR AN ADVANCED COCHLEAR NUCLEUS AUDITORY PROSTHESIS

PSYCHOLOGICAL RISK FACTORS, QUALITY OF LIFE, COMMUNITY, AND BRAIN AGING IN AMERICAN INDIANS: THE STRONG HEART STUDY - PROJECT SUMMARY/ABSTRACT EVERY 65 SECONDS SOMEONE IN THE US IS DIAGNOSED WITH ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD). AMERICAN INDIAN (AI) ADULTS HAVE GREATER BURDEN OF CEREBROVASCULAR AND ADRD-RELATED COMORBIDITIES THAN THEIR NON-HISPANIC WHITE COUNTERPARTS. AI ADULTS ALSO SUFFER DISPROPORTIONATE STRESS AND TRAUMA, AND CONCOMITANT HIGH RATES OF DEPRESSION. RELATEDLY, AI ADULTS ALSO HAVE HIGH RATES OF SUBSTANCE MISUSE COMPARED TO OTHER RACIAL/ETHNIC GROUPS. THESE PUBLIC HEALTH PROBLEMS BECOME EXACERBATED AS A POPULATION AGES, SINCE STRESS, DEPRESSION AND SUBSTANCE USE HAVE BEEN LINKED TO COGNITIVE IMPAIRMENT LATER IN LIFE. FORTUNATELY, IMPROVEMENTS TO HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND COMMUNITY CONNECTEDNESS MAY AMELIORATE THESE NEGATIVE IMPACTS, ALTHOUGH NONE OF THESE ASSOCIATIONS HAVE BEEN FULLY EVALUATED IN AI ADULTS. AS IMPAIRED COGNITIVE PERFORMANCE PRECEDES DEVELOPMENT OF ADRD, WE WILL DETERMINE RISK AND PROTECTIVE FACTORS OF COGNITIVE PERFORMANCE IN AI ADULTS TO INFORM PREVENTION STRATEGIES TO POTENTIALLY CIRCUMVENT LATER DEVELOPMENT OF ADRD. LONGITUDINAL RELATIONSHIPS BETWEEN PSYCHOLOGICAL RISK FACTORS AND COGNITIVE IMPAIRMENT NEED TO BE DIRECTLY EVALUATED TO EXAMINE THE TEMPORAL SEQUENCE OF CLINICAL CHANGES THAT OCCUR WITH AGING. ADDITIONALLY, RESEARCH TESTING THE LONGITUDINAL RELATIONSHIP WITH COGNITIVE PERFORMANCE AND DEMENTIA IN AI ADULTS IS MISSING. ESTABLISHED, LONGITUDINAL COHORT STUDIES OFFER OPPORTUNITY TO ASSESS MODIFIABLE RISK AND PROTECTIVE FACTORS IN AGING ADULTS, WITH MULTIPLE DATA COLLECTIONS. GIVEN THESE GAPS IN KNOWLEDGE, OUR OBJECTIVES ARE TO TEST THE LONGITUDINAL RELATIONSHIP AMONG STRESS, DEPRESSION, AND SUBSTANCE USE (ALCOHOL, TOBACCO, PRESCRIPTION OPIOIDS) WITH COGNITIVE PERFORMANCE IN AI ADULTS, AND WHETHER HRQOL AND COMMUNITY CONNECTEDNESS MODERATE THESE RELATIONSHIPS. OUR CENTRAL HYPOTHESIS IS THAT HIGHER STRESS RESULTS IN HIGHER DEPRESSION, MORE SUBSTANCE USE AND ESPECIALLY MISUSE, AND THAT ALL THREE ARE ASSOCIATED WITH LOWER COGNITIVE SCORES, WHEREAS BETTER HRQOL AND BETTER COMMUNITY CONNECTEDNESS MODERATE THESE DELETERIOUS EFFECTS. USING THE PSYCHOMETRICALLY-ROBUST NIH TOOLBOX, WE WILL ALSO TEST AND DEVELOP NORMATIVE STANDARDS FOR THE AI COMMUNITY, MAKING IT POSSIBLE FOR THE FIRST TIME TO DIRECTLY COMPARE AI COGNITIVE DATA WITH NON-HISPANIC WHITE, ASIAN, AFRICAN-AMERICAN, AND HISPANIC ADULTS. OUR PROPOSED STUDY IS IN PARTNERSHIP WITH THE STRONG HEART STUDY, A 30-YEAR COHORT OF AGING AI ADULTS. WE PROPOSE TO COLLECT THESE PSYCHOLOGICAL AND COGNITIVE DATA IN A FOLLOW-UP EXAMINATION (N=3,000). DEFINING ASSOCIATIONS AMONG STRESS, DEPRESSION, SUBSTANCE MISUSE, HRQOL, AND COMMUNITY; AND DEFINING COGNITIVE STANDARDS IN A COMMONLY USED, ESTABLISHED PLATFORM WILL INFORM FUTURE PUBLIC HEALTH PREVENTION AND TREATMENT STRATEGIES FOR THIS UNDERSERVED, OVERBURDENED POPULATION.

NOVEL AUTONOMOUS ROLES OF CNS ANGIOGENESIS

SILICON-BASED MICROELECTRODE ARRAYS FOR NEUROPROSTHETIC CONTROL OF MICTURITION

ARRAYS FOR DEEP BRAIN MICROSTIMULATION AND RECORDING

ULTRA-FAST 15N IMAGING IN CHOLINE IN CANCER

13C AND 15N MRS STUDY OF GLUTAMATE CONTROL IN EPILEPSY

MR SPECTROSCOPY TO STUDY BRAIN GLUTAMATE IN HIV/AIDS AND METHAMPHETAMINE USERS

COGNITIVE CHALLENGE TO REVEAL PRESYMPTOMATIC ALZHEIMER'S DISEASE

DEVELOPMENT AND EVALUATION OF BIODEGRADABLE NEURAL PROBES

CHRONICALLY-IMPLANTABLE MULTISITE MICROELECTRODE ARRAYS

A CHIANG MAI UNIVERSITY - HMRI MRI/MRS PROJECT: A NEUROBIOLOGY STUDY OF METHAMPHE

SHARED RESOURCE IN CELLULAR IMAGING - ABSTRACT THE VISION OF THE CELLULAR IMAGING CORE OF THE HUNTINGTON MEDICAL RESEARCH INSTITUTES (HMRI) IS TO PROVIDE INVESTIGATORS ACCESS TO CUTTING-EDGE TECHNOLOGY, AND EXPERT TECHNICAL SUPPORT FOR MICROSCOPIC OBSERVATION AND ANALYSIS OF CELLULAR ANATOMY AND PHYSIOLOGY THAT IS ESSENTIAL FOR DIVERSE ASPECTS OF OUR MULTIDISCIPLINARY BIOMEDICAL RESEARCH. A MAJOR GAP IN OUR CURRENT IMAGING SYSTEMS IS ACQUIRING A BALANCE BETWEEN IMAGE QUALITY, THROUGHPUT, AND ACCESSIBILITY. DUE TO THESE LIMITATIONS, RESEARCHERS AT HMRI NEED TO OUTSOURCE THEIR BRIGHTFIELD AND IMMUNOFLUORESCENCE NEEDS TO COSTLY AND BUSY CORE FACILITIES. HERE WE PROPOSE TO OVERCOME THESE WORKFLOW AND HIGH-COST LIMITATIONS BY PROPOSING AN ALL-IN-ONE FLUORESCENCE MICROSCOPE, BZ-X800 THAT HAS MULTIPLE FEATURES AND WILL STRENGTHEN THE CELL BIOLOGY PROJECTS IN VARIOUS LABS AT HMRI. THE INSTRUMENT WILL BE HOUSED IN THE CELLULAR IMAGING CORE FACILITY DESIGNATED TO THE SECOND FLOOR OF THE NEWLY BUILT RESEARCH BUILDING AND WILL ACCELERATE RESEARCH SUPPORTED BY 5 NIH R01 GRANTS, ON ROBUST AND QUANTITATIVE FLUORESCENCE AND BRIGHTFIELD IMAGING. THE CORE WILL BE SHARED BY MULTIPLE INVESTIGATORS AND WILL STRENGTHEN THE UNDERGRADUATE, STEM AND POSTDOCTORAL EDUCATIONAL PROGRAMS AT HMRI. IT WILL BE CRITICAL FOR MEETING THE GOALS OF ONGOING NIH-FUNDED PROJECTS, AS WELL AS PLANNED FUTURE PROJECTS. THIS ALL-IN-ONE MICROSCOPE WILL FACILITATE OUR RESEARCH AT UNPRECEDENTED SPEEDS, AND FORGE NEW AVENUES FOR UNDERSTANDING AND TREATMENT OF PSYCHIATRIC, NEUROLOGICAL, AND HEART DISEASE.

MULTI-CHANNEL ELECTROCHEMICAL MEASUREMENT SYSTEM

NOVEL HYPERPOLARIZED C-13 AND N-15 BIOMARKERS FOR METABOLIC MR IMAGING OF CANCER

EARLY-CAREER PARTICIPANTS AT THE 4TH INTERNATIONAL CONFERENCE ON NEUROPROSTHETIC DEVICES ON NOVEMBER 19-20, 2012 AT THE UNIVERSITY OF FREIBURG, GERMA

EARLY-CAREER PARTICIPANTS AT THE 3RD INTERNATIONAL CONFERENCE ON NEUROPROSTHETIC DEVICES, SYDNEY AUSTRALIA, NOVEMBER 26-27, 2011

EARLY-CAREER PARTICIPANTS AT THE 2ND INTERNATIONAL CONFERENCE ON NEUROPROSTHETIC DEVICES FEBRUARY 27-28 2010 IN BEIJING CHINA